- Email: [email protected]
Monitoring corneal structures with slitlamp-adapted optical coherence tomography in laser in situ keratomileusis
Monitoring corneal structures with slitlampadapted optical coherence tomography in laser in situ keratomileusis Christopher Wirbelauer, MD, Duy Thoai Pham, MD Purpose: To monitor corneal structures with slitlamp-adapted optical coherence tomography (OCT) in laser in situ keratomileusis (LASIK). Setting: Department of Ophthalmology, Vivantes Klinikum Neuko¨lln, Berlin, Germany. Methods: In this prospective, nonrandomized, comparative clinical case series of consecutive patients who had LASIK for myopia and myopic astigmatism, the corneal structures were studied with slitlamp-adapted OCT at a wavelength of 1310 nm. The central corneal thickness (CCT) and epithelial, flap, and residual stromal thicknesses were assessed preoperatively, immediately after surgery, on postoperative day 1, and then, on average, after 8, 35, and 160 days. Results: Twenty-five eyes of 13 patients were included. The attempted mean spherical equivalent correction was ⫺6.11 diopters (D) ⫾ 2.16 (SD) with a mean calculated stromal ablation depth of 92 ⫾ 24 m. The CCT was 516 ⫾ 26 m preoperatively and 453 ⫾ 40 m postoperatively (P⬍.001). The epithelial thickness increased from 57.0 ⫾ 7.7 m preoperatively to 61.0 ⫾ 7.5 m postoperatively (P ⫽ .04). Imaging of the hyperreflective interface was possible in all patients for up to 15 months. The flap and residual stromal thickness was 211 ⫾ 28 m and 344 ⫾ 48 m, respectively, immediately after LASIK and 164 ⫾ 21 m (P⬍.001) and 284 ⫾ 32 m (P⬍.001), respectively, on postoperative day 1. There were no further significant changes during the follow-up. The overall mean reproducibility was ⫾4.50 m (coefficient of variation [CV] 0.94%) for CCT, ⫾4.99 m (CV 8.57%) for epithelial thickness, ⫾6.25 m (CV 3.55%) for flap thickness, and ⫾7.09 m (CV 2.42%) for residual stromal thickness. Conclusion: Slitlamp-adapted OCT can be used to longitudinally monitor the variable structures of the cornea, epithelium, flap, and residual stroma in LASIK. J Cataract Refract Surg 2004; 30:1851–1860 2004 ASCRS and ESCRS
L
aser in situ keratomileusis (LASIK) is the most common corneal refractive procedure involving the use of a microkeratome to create a corneal flap through Accepted for publication January 22, 2004. From Klinik fu¨r Augenheilkunde, Vivantes Klinikum Neuko¨lln, Berlin, Germany. Supported by Herbert Funke-Stiftung, Berlin, Germany. Neither author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Christopher Wirbelauer, MD, Klinik fu¨r Augenheilkunde, Vivantes Klinikum Neuko¨lln, Rudower Strasse 48, D-12351 Berlin, Germany. E-mail: [email protected]. 2004 ASCRS and ESCRS Published by Elsevier Inc.
a lamellar cut and an excimer laser to ablate the exposed stromal tissue. It is safe and effective and considered the procedure of choice to correct moderate to severe myopia and myopic astigmatism.1 Examination of corneal thickness is essential in LASIK, and the problem of corneal ectasia is gaining more attention.2–9 Recent reports demonstrate there is high variability in flap thickness after the microkeratome pass.10–14 Evaluation of the corneal cross-section in LASIK has been performed with acoustic methods such as highresolution ultrasound (US) biomicroscopy15 and optical systems such as confocal microscopy16–19 and retinal optical coherence tomography (OCT) at 840 nm.20,21 Re0886-3350/04/$–see front matter doi:10.1016/j.jcrs.2004.01.035
MONITORING CORNEAL STRUCTURES WITH OCT IN LASIK
cently, a slitlamp-adapted OCT system specifically designed for anterior segment imaging was used to assess the cornea experimentally,22 in normal eyes,23,24 in corneal diseases,25 and after photorefractive keratectomy (PRK).26 This method allowed precise cross-sectional morphometric corneal measurements with improved spatial resolution. In this clinical study, we used slitlamp-adapted OCT at a wavelength of 1310 nm to monitor corneal structures in LASIK.
Patients and Methods Patients and Clinical Examination This prospective, nonrandomized, comparative clinical case series comprised consecutive patients who had myopia and myopic astigmatism. Eligibility and exclusion criteria have been reported.26 An informed consent was obtained from each patient, and all were treated in accordance with the tenets of the Declaration of Helsinki. A complete preoperative ophthalmologic examination was performed in each patient including uncorrected (UCVA) and best corrected (BCVA) visual acuity measured in decimal fraction, manifest and cycloplegic refractions, autorefractometer (Speedy-K, Nikon), videokeratography (C-Scan, Technomed), noncontact endothelial cell microscopy (SP-2000P, Topcon), contact US pachymetry (Pocket Pachymeter, Quantel Medical), slitlamp biomicroscopy, Schirmer test, applanation tonometry, and indirect ophthalmoscopy. To determine the mean visual acuity, the logarithm of each value was calculated and the antilogarithm of this mean was used. For a preoperative distance visual acuity worse than 0.05, a value of 0.01 was used. Before each treatment, the scanning-spot excimer laser unit (Esiris, Schwind) was calibrated according to the manufacturer’s instructions and the instrument-specific stromal ablation depth was calculated. In all patients, an identical standardized surgical procedure with a superiorly hinged flap was performed using an automated oscillating microkeratome with an intended incision depth of 160 m and a flap diameter of 9.0 to 9.5 mm (Supratome, Schwind). The ablation zone ranged from 5.5 to 7.0 mm; most cases were treated with a 6.5 mm zone. The flap was repositioned at the conclusion of laser treatment with irrigation of the stromal bed to remove debris and epithelial cells, and the corneal surface was wiped with a moistened sponge.27 Flap alignment was verified, the peripheral gutters were inspected, and a 2-minute adherence time was allowed. Postoperatively, patients were treated with ofloxacin (Floxal威) 5 times daily for 1 week, dexamethasone 0.1% (Dexa-sine威) 5 times daily for 2 weeks, and topical lubricants for 4 weeks to 3 months as needed. A protective eye shield was provided for nighttime wear for 1 week. 1852
Slitlamp-Adapted Corneal OCT The cornea of each patient or specimen was examined with a slitlamp-adapted OCT system (AS-OCT, 4Optics AG). This clinical medical device was in conformity with the essential requirements based on certificates DIN EN ISO 9001, DIN EN ISO 46001, and DIN EN ISO 13485. To enhance the OCT image of the anterior segment, a light source using a superluminescent diode (SLD-561, Superlum) at a wavelength of 1310 nm with a bandwidth of 50 nm and incident light intensity of less than 200 W was used.22 This corresponded to a longitudinal resolution in air of 15 m, corresponding to approximately 11 m in corneal tissue. The sample arm of the interferometer and the scanning module were integrated in the projected slit of a standard clinical slitlamp (SL-3C, Topcon), as previously described.22–26 This enabled reliable adjustment of the OCT infrared light on the structures to be examined. The imaging capabilities of the flap and interface with corneal OCT in LASIK were confirmed in preliminary experimental studies in porcine eyes (Figure 1). All measurements were performed perpendicularly to the imaged central corneal site to avoid distortions, and all examinations were performed the same time of day (between 2 PM and 5 PM) to reduce the influence of circadian corneal thickness changes. For the tomographic representation of the cornea, the reflected light was analyzed and the intensity was converted to logarithmic gray-scale images, which were simultaneously recorded during the measurements. The total acquisition time depended on the line-scan frequency of 60 Hz and on the variable range of scans from 100 to 400 Hz. The focus diameter of the measurement beam was 20 m, the lateral width of the scan was 6.0 mm, and the depth of each scan in air was 2.0 mm with a scanning data acquisition time of 2 seconds. The resulting cross-sectional tomographic images had 360 pixels ⫻ 200 pixels with a digital sampling increment of 5.6 m axially and 30.0 m laterally. The lateral resolution was limited by the separation between 2 adjacent scans on the cornea and the total scan width. Slitlamp-adapted OCT facilitated determination of corneal structure thickness using the axial interference profile of the corneal reflections. All images were evaluated with specific software for analysis of the reflection profile (OCTeval, version 1.1, 4Optics AG). The high-detection sensitivity was used to manually measure the distance between the optical signals, with the highest reflectivity at the tissue boundaries. The corneal optical delay values obtained were divided by the group refractive index (n ⫽ 1.3853) to obtain the geometric distances between the tissue interfaces.24–26 The cross-sectional OCT image with the best quality was further analyzed, and 3 central measurements were performed within an area of ⫾500 m. The mean value and SD of these 3 measurements were further processed. The following critical values for LASIK were considered: total corneal thickness, epithelial thickness, flap thickness, and absolute (m) and relative (percentage of preoperative
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Figure 1. (Wirbelauer)
Slitlamp-adapted corneal OCT (gray scale) in experimental LASIK. a: Imaging of the flap after the microkeratome cut and optical changes with increased light reflectivity at the interface (arrow). b: Imaging after lifting the flap with visualization of the hinge (arrow).
corneal thickness) residual stromal thickness. Optical coherence tomography examinations were performed preoperatively, immediately postoperatively during flap alignment verification (35 minutes ⫾ 14 [SD]), on day 1, after 8 ⫾ 2 days (range 5 to 14 days), 35 ⫾ 10 days (range 15 to 61 days), and 160 ⫾ 100 days (range 60 to 472 days). The longest follow-up was 472 days or 15 months. To assess the risk factors involved in a postoperative CCT less than 430 m or a residual stromal thickness less than 250 m, the cumulative values of all postoperative OCT measurements except the immediate postoperative values were calculated; this corresponded to 95 measurements.
Statistical Analysis All results were presented as mean ⫾ SD and range. Changes were analyzed with the nonparametric Wilcoxon signed rank test. An ␣-level of 5% was chosen for comparison. Bonferroni adjustment was made for multiple testing, and a P value less than 0.005 was considered significant. The reproducibility was determined and an analysis of variance (coefficient of variation [CV]) performed. The CV values were calculated from the intrasession standard deviation for the 3 consecutive independent measurements against the mean value for each patient (SD ⫼ mean) and reported for all patients as an overall value.
Results Twenty-five eyes of 13 patients were included. The mean patient age was 37 ⫾ 11 years (range 22 to
66 years). The mean attempted spherical equivalent (SE) correction was ⫺6.11 ⫾ 2.16 diopters (D) (range ⫺2.50 to ⫺10.00 D) (Table 1). The mean nominal stromal ablation depth was 92 ⫾ 24 m (range 40 to 131 m). Twenty-three eyes had no astigmatic correction, and 2 eyes had attempted cylinder corrections of ⫺1.50 D and ⫺3.00 D. All but 2 eyes were corrected for full distance visual acuity. Refractive Results The refractive results are shown in Table 2. An undercorrection of ⫺4.50 D was planned in 1 patient and in a second patient with high preoperative astigmatism, although the keratometric cylinder increased and the manifest SE refraction decreased. One patient had to be retreated because of an undercorrection of ⫺1.50 D in the postoperative SE manifest refraction. Visual Acuity The UCVA and BCVA results are shown in Table 2. There was no loss of BCVA lines after LASIK. Table 1. Surgical data. Parameter
Mean ⫾ SD (Range)
Refractive correction (SE) (D)
⫺6.11 ⫾ 2.16 (⫺2.5 to ⫺10.0)
Ablation depth (m)
92 ⫾ 24
(40 to 131)
Ablation time (s)
89 ⫾ 29
(35 to 144)
Ablation layers (n)
252 ⫾ 74
(114 to 401)
SE ⫽ spherical equivalent
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Table 2. Refractive data. Examination Time Parameter
Preoperative
5 Mo Postoperative
P Value*
UCVA
0.02 ⫾ 0.03
(0.01 to 0.1)
0.53 ⫾ 0.33
(0.05 to 1.25)
⬍.001
BCVA
0.91 ⫾ 0.14
(0.5 to 1.0)
0.93 ⫾ 0.18
(0.5 to 1.25)
.364
Refraction (SE) (D)
⫺6.58 ⫾ 2.94
(⫺2.9 to ⫺14.5)
⫺0.94 ⫾ 1.10
(0.25 to ⫺5.25)
⬍.001
Keratometric power (D)
43.98 ⫾ 1.81
(39.25 to 46.0)
39.91 ⫾ 2.52
(33.62 to 44.75)
⬍.001
Keratometric cylinder (D)
⫺1.14 ⫾ 1.06
(⫺0.25 to ⫺5.62)
⫺1.29 ⫾ 1.65
(⫺0.25 to ⫺8.75)
.637
Means ⫾ SDs BCVA ⫽ best corrected visual acuity; SE ⫽ spherical equivalent; UCVA ⫽ uncorrected visual acuity *P⬍.005 compared with preoperative values (Wilcoxon signed ranks test)
Complications No vision-threatening complication occurred. A corneal erosion was noted in 1 patient after the microkeratome pass; it healed with mild haze formation. (The day-1 OCT measurements in this patient were excluded.) Flap microstriae were noted in 1 patient. At 3 months, 1 patient was retreated for an undercorrection. Serial videokeratography examinations did not detect significant decentration or keratectasia during the follow-up. Corneal OCT in LASIK The mean preoperative CCT with US pachymetry was 539 ⫾ 29 m (range 494 to 606 m) and decreased significantly to 466 ⫾ 42 m (range 398 to 531 m) postoperatively (P⬍.001). With corneal OCT, the mean preoperative CCT was 516 ⫾ 26 m (range 473 to 562 m) and the epithelial thickness, 57.0 ⫾ 5.7 m (range 48.0 to 78.0 m) (Table 3; Figure 2, A). Approximately 35 minutes after LASIK, marked swelling and increased thickness of the cornea was noted (Table 3; Figures 2, B, and 3). The CCT was 555 ⫾ 47 m (range 462 to 633 m), which corresponded to a mean increase of 7.6% (P⬍.001) (Table 3, Figure 3). The epithelial thickness remained unchanged (P ⫽ .27). The optically determined mean flap thickness was 211 ⫾ 28 m (range 173 to 274 m) and the residual stromal thickness, 344 ⫾ 48 m (range 275 to 438 m). On the first postoperative day, the CCT stabilized at 448 ⫾ 39 m (range 392 to 509 m), a significant decrease compared with preoperative (P⬍.001) and immediate postoperative (P⬍.001) measurements (Table 3; Figures 2, C, and 3). The mean CCT reduction compared with preoperative measurements was 66 ⫾ 1854
21 m (27 to 101 m) or 13.0% ⫾ 4.4% (5.3% to 20.5%). This corresponded to lower mean values than the calculated ablation depth of 26 m. The mean epithelial thickness was 55.0 ⫾ 6.3 m (range 43.0 to 68.0 m; P ⫽ .14). The flap and residual stromal thickness decreased significantly compared with immediately postoperatively to mean values of 164 ⫾ 21 m (range 112 to 209 m) and 284 ⫾ 32 m (215 to 339 m), respectively (P⬍.001) (Table 3, Figure 3). At later examinations, the corneal, flap, and residual stromal thicknesses remained stable with no significant changes (Table 3, Figure 3). The epithelial thickness showed a slight but significant increase of 6 m (P⬍.001) after 5 months compared with the values on day 1 (Table 3). At 5 months, the mean residual stromal thickness was 282 ⫾ 36 m (212 to 350 m) corresponding to a relative residual stroma of 55.0% ⫾ 5.2% (range 43.0% to 64.0%). Although no patient had a residual stromal thickness less than 200 m during the follow-up, 7 eyes had a residual stromal thickness less than 250 m on corneal OCT measurement. Cumulative risk factors showed that eyes with a postoperative OCT corneal thickness less than 430 m (34 measurements, 36% of cases) were primarily those with a preoperative OCT corneal thickness below 500 m (82%) and had a 56% chance of a residual stromal thickness less than 250 m at a mean flap thickness of 161 m (range 112 to 195 m). Eyes with a residual stromal thickness less than 250 m in corneal OCT (21 measurements, 22% of cases) were primarily those with a preoperative corneal thickness below 500 m (86%) or a postoperative corneal thickness less than 430 m (91%) with a mean flap thickness of 173 m (range 154 to 194 m). Corrections of more than 8.0 D were made in only 29% of these eyes.
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Table 3. Central corneal OCT values before and after LASIK. Examination Time, Mean ⫾ SD (Range) Parameter
Preoperative
35 Min
1D
8D
35 D
160 D
516 ⫾ 26 (473 to 562)
555 ⫾ 47† (462 to 633)
448 ⫾ 39†‡ (392 to 509)
445 ⫾ 40 (383 to 513)
450 ⫾ 36 (391 to 513)
453 ⫾ 40 (389 to 511)
⌬ CCT* (m)
—
40 ⫾ 30 (–32 to 84)
–66 ⫾ 21 (–27 to –101)
–71 ⫾ 22 (–24 to –109)
–64 ⫾ 21 (–19 to –103)
–63 ⫾ 22 (–22 to –101)
⌬ CCT* (%)
—
7.6 ⫾ 5.7 (–6.4 to 17.4)
–13 ⫾ 4.4 (–5.3 to –20.5)
–14 ⫾ 4.6 (–4.4 to –21.8)
–13 ⫾ 4.4 (–3.6 to –20.8)
–12 ⫾ 4.5 (–4.3 to 20.1)
57 ⫾ 7.7 (48 to 78)
59 ⫾ 7.3 (49 to 76)
55 ⫾ 6.3 (43 to 68)
59 ⫾ 7.9 (48 to 78)
61 ⫾ 8.1 (43 to 78)
61 ⫾ 7.5‡ (46 to 79)
Flap (m)
—
211 ⫾ 28 (173 to 274)
164 ⫾ 21‡ (112 to 209)
168 ⫾ 18 (120 to 207)
169 ⫾ 15 (138 to 192)
171 ⫾ 21 (135 to 223)
Residual stroma (m)
—
344 ⫾ 48 (275 to 438)
284 ⫾ 32‡ (215 to 339)
276 ⫾ 38 (209 to 353)
281 ⫾ 39 (209 to 362)
282 ⫾ 36 (212 to 350)
Residual stroma (%)
—
67 ⫾ 6.9 (57 to 80)
55 ⫾ 4.4 (45 to 64)
53 ⫾ 5.7 (43 to 66)
55 ⫾ 5.4 (43 to 65)
55 ⫾ 5.2 (43 to 64)
CCT (m)
Epithelium (m)
Means ⫾ SDs CCT ⫽ central corneal thickness; LASIK ⫽ laser in situ keratomileusis; OCT ⫽ optical coherence tomography *Changes in the CCT compared to preoperatively † P⬍.005 compared with preoperative values (Wilcoxon signed rank test) ‡ P⬍.005 compared with 35 minutes or day 1 postoperative values (Wilcoxon signed rank test)
The mean reproducibility results of corneal OCT in LASIK are summarized in Table 4. Reproducibility was lowest for the determination of epithelial thickness. There was a transient slight decrease in reproducibility in all measurements of the corneal structures in the immediate postoperative period (Table 4).
Discussion Laser in situ keratomileusis involves the use of a microkeratome to create a thin lamellar corneal flap followed by excimer laser ablation of the corneal stroma and repositioning of the flap. Since refractive surgery candidates are healthy and have correctable vision, key criteria of LASIK are high standards of safety and stability and prevention of corneal complications by careful patient selection and therapeutic planning.1 Corneal imaging before and after LASIK is extremely important. Two-dimensional high-resolution imaging of the corneal structures after LASIK has been described with high-frequency US15 and confocal microscopy,16–19 but these are relatively invasive contact methods requiring a contact gel or an immersion bath with an uncertain effect due to epithelial compression or edema. The individual anatomical variability of corneal flap thickness and corneal stromal changes after LASIK has
also been reported with a retinal OCT at a wavelength of 840 nm, but this has certain limitations.20,21 In this prospective investigation, we evaluated the clinical application of slitlamp-adapted OCT for noncontact monitoring of the longitudinal changes in the corneal layers in LASIK. This OCT system had a wavelength of 1310 nm as the light source and was specifically designed for anterior segment applications.22–26 Slitlamp-adapted OCT allowed a 6.0 mm wide scan over the corneal cross-section compared with 1.0 to 3.8 mm scans in previous studies with retinal OCT,20,21 which also permitted peripheral measurements in selected cases. A wavelength longer than 840 nm improved resolution and definition of the corneal optical interfaces because of higher scattering in the tissues. In this clinical evaluation, slitlamp-adapted OCT confirmed reliable imaging of the cornea, epithelial layer, flap, and residual stroma in LASIK. Interface imaging was crucial in determining flap and residual stromal thickness with corneal OCT. Although the amount of light reflectivity was not quantified, the observed OCT imaging properties of the interface were distinguishable as early and late features. The early imaging properties were caused by slight surface irregularities from the movement of the oscillating blade, which
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Figure 2. (Wirbelauer)
Slitlamp-adapted corneal OCT (gray scale) of a patient before and after LASIK (myopic correction ⫺5.0 D [SE], ablation depth 78 m). a: Preoperative corneal OCT with a central thickness of 517 m. b: Corneal OCT 40 minutes after LASIK revealing surgically induced stromal edema. The central thickness values were 566 m for the cornea, 207 m for the flap, and 359 m for the residual stroma. c: On the first postoperative day, the values stabilized with a CCT of 457 m, a flap thickness of 160 m, and a residual stromal thickness of 294 m. Arrows demonstrate the optical interface.
caused ultrastructural changes and increased light scattering from irregular collagen fibrils and collagen fragments.28–31 A higher flap⫺interface reflectivity from microfolds in Bowman’s layer and an increase in scattering particles has also been confirmed by confocal microscopy, which was able to resolve the intrastromal changes at the cellular level.16–19 The late OCT imaging properties after LASIK were related to wound repair, which is a complex process exhibiting activated keratocytes at the wound margin and deposition of extracellular matrix material adjacent to the interface.16–19,29 However, after LASIK, the intrastromal interface is optically less well-defined than other 1856
corneal structures; there is minimal stromal disorganization and wound healing at the flap margins in animal and human studies.29,32–34 This might affect OCT imaging capabilities and discrimination of the microkeratome cut because of variable light reflectivities. With a retinal OCT, difficulties in interface determination after LASIK have been noted in cases with increased stromal tissue light scattering or after longer follow-up, with a decrease in discrimination of the intrastromal interface over time.20 Comparing the axial light reflectivity profile with the 2-dimensional corneal OCT image allowed us to correlate reflectivity changes with the interface bound-
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detection of this corneal substructure. The flap and residual stromal thickness reproducibility were ⬍5% with no deterioration after 5 months, which seems to be sufficient in the clinical setting. The microkeratome unit used in this study was automated, based on the oscillating blade principle designed to produce a surface-parallel keratotomy. The mean OCT flap thickness on day 1 was 164 ⫾ 21 m, which correlated well with the planned incision depth. However, the thickest flap was 223 m and the actual flap thickness has been shown to vary considerably depending on the microkeratome used.10–14 This illustrates that assumptions based on calculation of the flap thickness only can be misleading. Although intraoperative studies with US show a lower than predicted flap thickness,10–14 other studies with confocal microscopy report higher values for the same microkeratomes in the postoperative period.16,19 Thus, it seems there are marked differences between intraoperative and postoperative measurements10–14,37 and compression during suction and cutting may lead to lower flap thickness values intraoperatively. This was confirmed by a recent intraoperative study with online optical coherence pachymetry using the same microkeratome.27 In late postoperative measurements, the OCT flap thickness increased slightly by, on average, 7 m, but these changes were not significant. This contrasts with the partial regression and significant flap thickness increase noted with confocal microscopy,16 which was partly due to an increase in epithelial thickness. This is the only longitudinal study describing early postoperative changes immediately after LASIK. Noncontact OCT allowed us to study the immediate effects on the microstructure of the cornea without interfering with postoperative flap position and alignment. The OCT thickness values immediately after LASIK revealed
Figure 3. (Wirbelauer) The longitudinal OCT thickness changes of the cornea, epithelium, flap, and residual stroma in LASIK (mean ⫾ SD). Asterisks depict significant changes (P⬍.001) compared with preoperative (*) and immediately postoperative and day 1 (**) values.
aries and thus prevent higher variability in optical detection and a decrease in detection sensitivity. After LASIK, the interface was visible in all eyes for up to 15 months with good reproducibility; with retinal OCT, there was no visualization and an increase in failed measurements in 9.5% of eyes after 3 months.20 However, interface position variability and possible inclusion of the posterior border of the flap or the anterior border of the residual stroma in the thickness measurements must be considered. In our study, corneal reproducibility of slitlampadapted OCT at a wavelength of 1310 nm was similar to that with an OCT system at 830 nm.24 However, with OCT the CCT values were lower than those measured with US pachymetry, which is related to the differences between the refractive index and the speed of sound in corneal tissue.24 The epithelial reproducibility was better than at a wavelength of 830 nm,35,36 which indicates that a wavelength of 1310 nm improved the Table 4. Mean reproducibility of corneal OCT data in LASIK.
Examination Time Parameter
Preoperative
35 Min
1D
8D
35 D
160 D
Overall
CCT
4.90 (0.95)
5.09 (0.92)
3.76 (0.84)
4.19 (0.94)
5.04 (1.12)
4.02 (0.89)
4.50 (0.94)
Epithelium
3.24 (5.69)
7.54 (12.9)
5.92 (10.8)
4.8 (8.17)
4.03 (6.57)
4.44 (7.29)
4.99 (8.57)
Flap
7.34 (3.48)
6.82 (4.16)
5.63 (3.35)
4.97 (2.94)
6.50 (3.80)
6.25 (3.55)
Residual stroma
8.36 (2.43)
7.34 (2.59)
7.34 (2.66)
5.73 (2.04)
6.67 (2.37)
7.09 (2.42)
CCT ⫽ central corneal thickness; LASIK ⫽ laser in situ keratomileusis
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considerable corneal swelling from the microkeratome cut, surgical manipulations, and final irrigation procedures. The corneal hydration was linearly related to the corneal thickness, with a mean increase of 7.6% and a maximum swelling of 17.5%, but no significant changes in epithelial thickness. In some cases, the changes in stromal hydration interfered with the optical resolution of the corneal structures and interface visualization. However, rapid and complete recovery of the corneal values was noted on day 1. Contact-lens studies show that corneal deswelling measured with OCT occurs at a rate of approximately 5.6% per hour38 and deswelling from central corneal edema is 8.2% after 12 hours.39 Although changes in corneal hydration may affect the refractive index postoperatively40 and influence the measurements, the OCT values were relatively stable after day 1. This long-term stability of corneal OCT values after LASIK seems to allow a reliable assessment on day 1. Epithelial imaging with slitlamp-adapted OCT has been described.35,36 In our study, a small but significant increase in the anterior epithelial components was noted 5 months after LASIK compared with day 1, with no changes in the refractive results. After LASIK, a thickened epithelium was also found with confocal microscopy compared with normalized preoperative values19 found with a 50 MHz US pachymeter41 or other highresolution US techniques.15 Although post-LASIK epithelial thickening is lower than after surface ablation in PRK,42,43 corneal OCT could be important in studying epithelial and stromal factors involved in refractive regression after LASIK. Corneal OCT could also allow 2-dimensional visualization and quantification of intrastromal changes at the interface or interface complications such as diffuse lamellar keratitis, infection, epithelial ingrowth, and haze.36 Corneal OCT was also relevant in determining the amount of correction over the clinical course. On day 1, the measured ablation depth was significantly lower than the calculated depth by a mean of 26 m. Although the nominal ablation depth of the excimer laser can vary, these values are in contrast to intraoperative results27 and OCT values immediately after myopic PRK,26 in which the measured ablation depth is higher than the calculated ablation depth. The postoperative OCT results reveal that the presumed calculated ablation depth is probably lower, considering the postoperative corneal 1858
changes. This also confirms differences noted between the calculated magnitude of corneal surface change and the actual refraction change.40 The mean residual stromal thickness was 284 ⫾ 32 m on day 1, with no significant changes during the follow-up. An increase of 7.0 m in residual stromal thickness has been reported,20 but this increase could be related to a decrease in interface detection observed with retinal OCT. The lowest residual thickness in this study was 209 m; in 7 eyes, it was below 250 m with no clinical or topographic signs of corneal ectasia. Recent histological reports confirm that corneal ectasia, a major anatomical complication of LASIK, is caused by biomechanical corneal weakening after excessively deep central corneal ablation.5,7,34,44 Evaluation of the residual stromal thickness has been shown as crucial to prevent corneal ectasia, and safeguarding 250 m of stromal bed or 50% of the preoperative corneal thickness is the current standard of care to avoid this complication.2–4 Patients with lower residual stromal thickness measured intraoperatively by US pachymetry also had a higher posterior corneal elevation in LASIK enhancements.45 Ectasia has also occurred when more than 250 m of residual stroma remains,2,6 suggesting the phenomenon may be tissue dependent and involve metabolic processes.46 Of the reported cases of progressive corneal ectasia after LASIK, none had reliable measurements of residual bed thickness and multiple assumptions were required for estimating the values.2,3,5–7 Corneal OCT can supply the residual stromal thickness values to detect relevant biomechanical alterations and understand the corneal reactions after LASIK to prevent keratectasia. Major risk factors that could impair corneal stability are a cornea thinner than 500 m preoperatively, the flap thickness achieved by the microkeratome cut, a postoperative corneal thickness of less than 430 m, and refractive corrections greater than 8.0 D.2–9,37 In this study, the most common cumulative risk factors for a residual stromal thickness less than 250 m were a preoperative CCT less than 500 m or a postoperative corneal thickness less than 430 m. The flap thickness was not markedly increased in these eyes, and most had myopic corrections less than 8.0 D. Although studies with high-frequency US show that variability in the ability to predict residual stromal layer thickness postoperatively might be 30 m,47 our results indicate that
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in anatomically predisposed eyes, a residual stromal thickness of less than 250 m is probably more frequent than thought. This underscores the importance of a thorough preoperative evaluation and performing continuous intraoperative corneal thickness measurements during LASIK to avoid excessive thinning.27 In summary, slitlamp-adapted OCT allowed us to obtain preoperative and postoperative quantitative thicknesses of the cornea, epithelium, flap, and residual stroma in LASIK. Our study applied current knowledge about longitudinal changes in the corneal structures and helped in understanding the physiological effects and healing response of the cornea in LASIK. Comparing the optical thickness values of the corneal structures with the postoperative refraction may further improve surgeons’ LASIK nomograms, which seems particularly important in treating patients with thin corneas, performing LASIK enhancements, and planning high refractive corrections.
References 1. Sugar A, Rapuano CJ, Culbertson WW, et al. Laser in situ keratomileusis for myopia and astigmatism: safety and efficacy. (Ophthalmic Technologies Assessment) A report by the American Academy of Ophthalmology. Ophthalmology 2002; 109:175–187 2. Seiler T, Quurke AW. Iatrogenic keratectasia after LASIK in a case of forme fruste keratoconus. J Cataract Refract Surg 1998; 24:1007–1009 3. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ keratomileusis. J Refract Surg 1998; 14:312–317 4. Probst LE, Machat JJ. Mathematics of laser in situ keratomileusis for high myopia. J Cataract Refract Surg 1998; 24:190–195 5. Geggel HS, Talley AR. Delayed onset keratectasia following laser in situ keratomileusis. J Cataract Refract Surg 1999; 25:582–586 6. Amoils SP, Deist MB, Gous P, Amoils PM. Iatrogenic keratectasia after laser in situ keratomileusis for less than ⫺4.0 to ⫺7.0 diopters of myopia. J Cataract Refract Surg 2000; 26:967–977 7. Argento C, Cosentino MJ, Tytium A, et al. Corneal ectasia after laser in situ keratomileusis. J Cataract Refract Surg 2001; 27:1440–1448 8. Pallikaris IG, Kymionis GD, Astyrakakis NI. Corneal ectasia induced by laser in situ keratomileusis. J Cataract Refract Surg 2001; 27:1796–1802 9. Randleman JB, Russell B, Ward MA, et al. Risk factors and prognosis for corneal ectasia after LASIK. Ophthalmology 2003; 110:267–275
10. Pe´rez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg 1997; 23:372–385 11. Durairaj VD, Balentine J, Kouyoumdjian G, et al. The predictability of corneal flap thickness and tissue laser ablation in laser in situ keratomileusis. Ophthalmology 2000; 107:2140–2143 12. Yildirim R, Aras C, Ozdamar A, et al. Reproducibility of corneal flap thickness in laser in situ keratomileusis using the Hansatome microkeratome. J Cataract Refract Surg 2000; 26:1729–1732 13. Shemesh G, Dotan G, Lipshitz I. Predictability of corneal flap thickness in laser in situ keratomileusis using three different microkeratomes. J Refract Surg 2002; 18:S347–S351 14. Spadea L, Cerrone L, Necozione S, Balestrazzi E. Flap measurements with the Hansatome microkeratome. J Refract Surg 2002; 18:149–154 15. Reinstein DZ, Silverman RH, Raevsky T, et al. Arcscanning very high-frequency digital US for 3D pachymetric mapping of the corneal epithelium and stroma in laser in situ keratomileusis. J Refract Surg 2000; 16:414–430 16. Vesaluoma M, Pe´rez-Santonja J, Petroll WM, et al. Corneal stromal changes induced by myopic LASIK. Invest Ophthalmol Vis Sci 2000; 41:369–376; erratum, 2027 17. Pisella P-J, Auzerie O, Bokobza Y, et al. Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with confocal microscopy. Ophthalmology 2001; 108:1744–1750 18. Erie JC, Patel SV, McLaren JW, et al. Effect of myopic laser in situ keratomileusis on epithelial and stromal thickness; a confocal microscopy study. Ophthalmology 2002; 109:1447–1452 19. Gokmen F, Jester JV, Petroll WM, et al. In vivo confocal microscopy through-focusing to measure corneal flap thickness after laser in situ keratomileusis. J Cataract Refract Surg 2002; 28:962–970 20. Maldonado MJ, Ruiz-Oblitas L, Munuera JM, et al. Optical coherence tomography evaluation of the corneal cap and stromal bed features after laser in situ keratomileusis for high myopia and astigmatism. Ophthalmology 2000; 107:81–87; discussion by DR Hardten, 88 21. Ustundag C, Bahcecioglu H, Ozdamar A, et al. Optical coherence tomography for evaluation of anatomical changes in the cornea after laser in situ keratomileusis. J Cataract Refract Surg 2000; 26:1458–1462 22. Wirbelauer C, Winkler J, Scholz C, et al. Experimental imaging of intracorneal ring segments with optical coherence tomography. J Refract Surg 2003; 19:367–371 23. Wirbelauer C, Scholz C, Hoerauf H, et al. Untersuchungen der Hornhaut mittels optischer Koha¨renztomographie. Ophthalmologe 2001; 98:151–156 24. Wirbelauer C, Scholz C, Hoerauf H, et al. Noncontact corneal pachymetry with slit lamp-adapted optical coher-
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ence tomography. Am J Ophthalmol 2002; 133:444– 450 Wirbelauer C, Winkler J, Bastian GO, et al. Histopathological correlation of corneal diseases with optical coherence tomography. Graefe’s Arch Clin Exp Ophthalmol 2002; 240:727–734 Wirbelauer C, Scholz C, Hoerauf H, et al. Corneal optical coherence tomography before and immediately after excimer laser photorefractive keratectomy. Am J Ophthalmol 2000; 130:693–699 Wirbelauer C, Pham DT. Intraoperative optical coherence pachymetry during laser in situ keratomileusis—first clinical experience. J Refract Surg 2003; 19: 372–377 Behrens A, Langenbucher A, Kus MM, et al. Experimental evaluation of two current-generation automated microkeratomes: the Hansatome and the Supratome. Am J Ophthalmol 2000; 129:59–67 Rumelt S, Cohen I, Skandarani P, et al. Ultrastructure of the lamellar corneal wound after laser in situ keratomileusis in human eye. J Cataract Refract Surg 2001; 27:1323–1327 Anderson NJ, Edelhauser HF, Sharara N, et al. Histologic and ultrastructural findings in human corneas after successful laser in situ keratomileusis. Arch Ophthalmol 2002; 120:288–293 Hamill MB, Kohnen T. Scanning electron microscopic evaluation of the surface characteristics of 4 microkeratome systems in human corneas. J Cataract Refract Surg 2002; 28:328–336 Amm M, Wetzel W, Winter M, et al. Histopathological comparison of photorefractive keratectomy and laser in situ keratomileusis in rabbits. J Refract Surg 1996; 12: 758–766 Park CK, Kim JH. Comparison of wound healing after photorefractive keratectomy and laser in situ keratomileusis in rabbits. J Cataract Refract Surg 1999; 25:842– 850 Philipp WE, Speicher L, Go¨ttinger W. Histological and immunohistochemical findings after laser in situ keratomileusis in human corneas. J Cataract Refract Surg 2003; 29:808–820 Wirbelauer C, Scholz C, Engelhardt R, et al. Biomorphometrie des Hornhautepithels mittels spaltlampenadap-
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tierter optischer Koha¨renztomographie. Ophthalmologe 2001; 98:848–852 Wirbelauer C, Scholz C, Ha¨berle H, et al. Corneal optical coherence tomography before and after phototherapeutic keratectomy for recurrent epithelial erosions. J Cataract Refract Surg 2002; 28:1629–1635 Lee D-H, Seo S, Jeong KW, et al. Early spatial changes in posterior corneal surface after laser in situ keratomileusis. J Cataract Refract Surg 2003; 29:778–784 Wang J, Fonn D, Simpson TL, Jones L. Relation between optical coherence tomography and optical pachymetry measurements of corneal swelling induced by hypoxia. Am J Ophthalmol 2002; 134:93–98 Holden BA, Mertz GW, McNally JJ. Corneal swelling response to contact lenses worn under extended wear conditions. Invest Ophthalmol Vis Sci 1983; 24:218– 226 Patel S, Alio´ JL, Pe´rez-Santonja JJ. A model to explain the difference between changes in refraction and central ocular surface power after laser in situ keratomileusis. J Refract Surg 2000; 16:330–335 Spadea L, Fasciani R, Necozione S, Balestrazzi E. Role of the corneal epithelium in refractive changes following laser in situ keratomileusis for high myopia. J Refract Surg 2000; 16:133–139 Gauthier CA, Holden BA, Epstein D, et al. Role of epithelial hyperplasia in regression following photorefractive keratectomy. Br J Ophthalmol 1996; 80:545– 548 Lohmann CP, Reischl U, Marshall J. Regression and epithelial hyperplasia after myopic photorefractive keratectomy in a human cornea. J Cataract Refract Surg 1999; 25:712–715 Jabbur NS, Stark WJ, Green WR. Corneal ectasia after laser-assisted in situ keratomileusis. Arch Ophthalmol 2001; 119:1714–1716 Rani A, Murthy BR, Sharma N, et al. Posterior corneal topographic changes after retreatment LASIK. Ophthalmology 2002; 109:1991–1995 Comaish IF, Lawless MA. Progressive post-LASIK keratectasia; biomechanical instability or chronic disease process? J Cataract Refract Surg 2002; 28:2206–2213 Reinstein DZ, Srivannaboon S, Sutton HFS, et al. Risk of ectasia in LASIK: revised safety criteria (ARVO abstract #2121). Invest Ophthalmol Vis Sci 1999; 40(4): S403
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L
aser in situ keratomileusis (LASIK) is the most common corneal refractive procedure involving the use of a microkeratome to create a corneal flap through Accepted for publication January 22, 2004. From Klinik fu¨r Augenheilkunde, Vivantes Klinikum Neuko¨lln, Berlin, Germany. Supported by Herbert Funke-Stiftung, Berlin, Germany. Neither author has a financial or proprietary interest in any material or method mentioned. Reprint requests to Christopher Wirbelauer, MD, Klinik fu¨r Augenheilkunde, Vivantes Klinikum Neuko¨lln, Rudower Strasse 48, D-12351 Berlin, Germany. E-mail: [email protected]. 2004 ASCRS and ESCRS Published by Elsevier Inc.
a lamellar cut and an excimer laser to ablate the exposed stromal tissue. It is safe and effective and considered the procedure of choice to correct moderate to severe myopia and myopic astigmatism.1 Examination of corneal thickness is essential in LASIK, and the problem of corneal ectasia is gaining more attention.2–9 Recent reports demonstrate there is high variability in flap thickness after the microkeratome pass.10–14 Evaluation of the corneal cross-section in LASIK has been performed with acoustic methods such as highresolution ultrasound (US) biomicroscopy15 and optical systems such as confocal microscopy16–19 and retinal optical coherence tomography (OCT) at 840 nm.20,21 Re0886-3350/04/$–see front matter doi:10.1016/j.jcrs.2004.01.035
MONITORING CORNEAL STRUCTURES WITH OCT IN LASIK
cently, a slitlamp-adapted OCT system specifically designed for anterior segment imaging was used to assess the cornea experimentally,22 in normal eyes,23,24 in corneal diseases,25 and after photorefractive keratectomy (PRK).26 This method allowed precise cross-sectional morphometric corneal measurements with improved spatial resolution. In this clinical study, we used slitlamp-adapted OCT at a wavelength of 1310 nm to monitor corneal structures in LASIK.
Patients and Methods Patients and Clinical Examination This prospective, nonrandomized, comparative clinical case series comprised consecutive patients who had myopia and myopic astigmatism. Eligibility and exclusion criteria have been reported.26 An informed consent was obtained from each patient, and all were treated in accordance with the tenets of the Declaration of Helsinki. A complete preoperative ophthalmologic examination was performed in each patient including uncorrected (UCVA) and best corrected (BCVA) visual acuity measured in decimal fraction, manifest and cycloplegic refractions, autorefractometer (Speedy-K, Nikon), videokeratography (C-Scan, Technomed), noncontact endothelial cell microscopy (SP-2000P, Topcon), contact US pachymetry (Pocket Pachymeter, Quantel Medical), slitlamp biomicroscopy, Schirmer test, applanation tonometry, and indirect ophthalmoscopy. To determine the mean visual acuity, the logarithm of each value was calculated and the antilogarithm of this mean was used. For a preoperative distance visual acuity worse than 0.05, a value of 0.01 was used. Before each treatment, the scanning-spot excimer laser unit (Esiris, Schwind) was calibrated according to the manufacturer’s instructions and the instrument-specific stromal ablation depth was calculated. In all patients, an identical standardized surgical procedure with a superiorly hinged flap was performed using an automated oscillating microkeratome with an intended incision depth of 160 m and a flap diameter of 9.0 to 9.5 mm (Supratome, Schwind). The ablation zone ranged from 5.5 to 7.0 mm; most cases were treated with a 6.5 mm zone. The flap was repositioned at the conclusion of laser treatment with irrigation of the stromal bed to remove debris and epithelial cells, and the corneal surface was wiped with a moistened sponge.27 Flap alignment was verified, the peripheral gutters were inspected, and a 2-minute adherence time was allowed. Postoperatively, patients were treated with ofloxacin (Floxal威) 5 times daily for 1 week, dexamethasone 0.1% (Dexa-sine威) 5 times daily for 2 weeks, and topical lubricants for 4 weeks to 3 months as needed. A protective eye shield was provided for nighttime wear for 1 week. 1852
Slitlamp-Adapted Corneal OCT The cornea of each patient or specimen was examined with a slitlamp-adapted OCT system (AS-OCT, 4Optics AG). This clinical medical device was in conformity with the essential requirements based on certificates DIN EN ISO 9001, DIN EN ISO 46001, and DIN EN ISO 13485. To enhance the OCT image of the anterior segment, a light source using a superluminescent diode (SLD-561, Superlum) at a wavelength of 1310 nm with a bandwidth of 50 nm and incident light intensity of less than 200 W was used.22 This corresponded to a longitudinal resolution in air of 15 m, corresponding to approximately 11 m in corneal tissue. The sample arm of the interferometer and the scanning module were integrated in the projected slit of a standard clinical slitlamp (SL-3C, Topcon), as previously described.22–26 This enabled reliable adjustment of the OCT infrared light on the structures to be examined. The imaging capabilities of the flap and interface with corneal OCT in LASIK were confirmed in preliminary experimental studies in porcine eyes (Figure 1). All measurements were performed perpendicularly to the imaged central corneal site to avoid distortions, and all examinations were performed the same time of day (between 2 PM and 5 PM) to reduce the influence of circadian corneal thickness changes. For the tomographic representation of the cornea, the reflected light was analyzed and the intensity was converted to logarithmic gray-scale images, which were simultaneously recorded during the measurements. The total acquisition time depended on the line-scan frequency of 60 Hz and on the variable range of scans from 100 to 400 Hz. The focus diameter of the measurement beam was 20 m, the lateral width of the scan was 6.0 mm, and the depth of each scan in air was 2.0 mm with a scanning data acquisition time of 2 seconds. The resulting cross-sectional tomographic images had 360 pixels ⫻ 200 pixels with a digital sampling increment of 5.6 m axially and 30.0 m laterally. The lateral resolution was limited by the separation between 2 adjacent scans on the cornea and the total scan width. Slitlamp-adapted OCT facilitated determination of corneal structure thickness using the axial interference profile of the corneal reflections. All images were evaluated with specific software for analysis of the reflection profile (OCTeval, version 1.1, 4Optics AG). The high-detection sensitivity was used to manually measure the distance between the optical signals, with the highest reflectivity at the tissue boundaries. The corneal optical delay values obtained were divided by the group refractive index (n ⫽ 1.3853) to obtain the geometric distances between the tissue interfaces.24–26 The cross-sectional OCT image with the best quality was further analyzed, and 3 central measurements were performed within an area of ⫾500 m. The mean value and SD of these 3 measurements were further processed. The following critical values for LASIK were considered: total corneal thickness, epithelial thickness, flap thickness, and absolute (m) and relative (percentage of preoperative
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Figure 1. (Wirbelauer)
Slitlamp-adapted corneal OCT (gray scale) in experimental LASIK. a: Imaging of the flap after the microkeratome cut and optical changes with increased light reflectivity at the interface (arrow). b: Imaging after lifting the flap with visualization of the hinge (arrow).
corneal thickness) residual stromal thickness. Optical coherence tomography examinations were performed preoperatively, immediately postoperatively during flap alignment verification (35 minutes ⫾ 14 [SD]), on day 1, after 8 ⫾ 2 days (range 5 to 14 days), 35 ⫾ 10 days (range 15 to 61 days), and 160 ⫾ 100 days (range 60 to 472 days). The longest follow-up was 472 days or 15 months. To assess the risk factors involved in a postoperative CCT less than 430 m or a residual stromal thickness less than 250 m, the cumulative values of all postoperative OCT measurements except the immediate postoperative values were calculated; this corresponded to 95 measurements.
Statistical Analysis All results were presented as mean ⫾ SD and range. Changes were analyzed with the nonparametric Wilcoxon signed rank test. An ␣-level of 5% was chosen for comparison. Bonferroni adjustment was made for multiple testing, and a P value less than 0.005 was considered significant. The reproducibility was determined and an analysis of variance (coefficient of variation [CV]) performed. The CV values were calculated from the intrasession standard deviation for the 3 consecutive independent measurements against the mean value for each patient (SD ⫼ mean) and reported for all patients as an overall value.
Results Twenty-five eyes of 13 patients were included. The mean patient age was 37 ⫾ 11 years (range 22 to
66 years). The mean attempted spherical equivalent (SE) correction was ⫺6.11 ⫾ 2.16 diopters (D) (range ⫺2.50 to ⫺10.00 D) (Table 1). The mean nominal stromal ablation depth was 92 ⫾ 24 m (range 40 to 131 m). Twenty-three eyes had no astigmatic correction, and 2 eyes had attempted cylinder corrections of ⫺1.50 D and ⫺3.00 D. All but 2 eyes were corrected for full distance visual acuity. Refractive Results The refractive results are shown in Table 2. An undercorrection of ⫺4.50 D was planned in 1 patient and in a second patient with high preoperative astigmatism, although the keratometric cylinder increased and the manifest SE refraction decreased. One patient had to be retreated because of an undercorrection of ⫺1.50 D in the postoperative SE manifest refraction. Visual Acuity The UCVA and BCVA results are shown in Table 2. There was no loss of BCVA lines after LASIK. Table 1. Surgical data. Parameter
Mean ⫾ SD (Range)
Refractive correction (SE) (D)
⫺6.11 ⫾ 2.16 (⫺2.5 to ⫺10.0)
Ablation depth (m)
92 ⫾ 24
(40 to 131)
Ablation time (s)
89 ⫾ 29
(35 to 144)
Ablation layers (n)
252 ⫾ 74
(114 to 401)
SE ⫽ spherical equivalent
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Table 2. Refractive data. Examination Time Parameter
Preoperative
5 Mo Postoperative
P Value*
UCVA
0.02 ⫾ 0.03
(0.01 to 0.1)
0.53 ⫾ 0.33
(0.05 to 1.25)
⬍.001
BCVA
0.91 ⫾ 0.14
(0.5 to 1.0)
0.93 ⫾ 0.18
(0.5 to 1.25)
.364
Refraction (SE) (D)
⫺6.58 ⫾ 2.94
(⫺2.9 to ⫺14.5)
⫺0.94 ⫾ 1.10
(0.25 to ⫺5.25)
⬍.001
Keratometric power (D)
43.98 ⫾ 1.81
(39.25 to 46.0)
39.91 ⫾ 2.52
(33.62 to 44.75)
⬍.001
Keratometric cylinder (D)
⫺1.14 ⫾ 1.06
(⫺0.25 to ⫺5.62)
⫺1.29 ⫾ 1.65
(⫺0.25 to ⫺8.75)
.637
Means ⫾ SDs BCVA ⫽ best corrected visual acuity; SE ⫽ spherical equivalent; UCVA ⫽ uncorrected visual acuity *P⬍.005 compared with preoperative values (Wilcoxon signed ranks test)
Complications No vision-threatening complication occurred. A corneal erosion was noted in 1 patient after the microkeratome pass; it healed with mild haze formation. (The day-1 OCT measurements in this patient were excluded.) Flap microstriae were noted in 1 patient. At 3 months, 1 patient was retreated for an undercorrection. Serial videokeratography examinations did not detect significant decentration or keratectasia during the follow-up. Corneal OCT in LASIK The mean preoperative CCT with US pachymetry was 539 ⫾ 29 m (range 494 to 606 m) and decreased significantly to 466 ⫾ 42 m (range 398 to 531 m) postoperatively (P⬍.001). With corneal OCT, the mean preoperative CCT was 516 ⫾ 26 m (range 473 to 562 m) and the epithelial thickness, 57.0 ⫾ 5.7 m (range 48.0 to 78.0 m) (Table 3; Figure 2, A). Approximately 35 minutes after LASIK, marked swelling and increased thickness of the cornea was noted (Table 3; Figures 2, B, and 3). The CCT was 555 ⫾ 47 m (range 462 to 633 m), which corresponded to a mean increase of 7.6% (P⬍.001) (Table 3, Figure 3). The epithelial thickness remained unchanged (P ⫽ .27). The optically determined mean flap thickness was 211 ⫾ 28 m (range 173 to 274 m) and the residual stromal thickness, 344 ⫾ 48 m (range 275 to 438 m). On the first postoperative day, the CCT stabilized at 448 ⫾ 39 m (range 392 to 509 m), a significant decrease compared with preoperative (P⬍.001) and immediate postoperative (P⬍.001) measurements (Table 3; Figures 2, C, and 3). The mean CCT reduction compared with preoperative measurements was 66 ⫾ 1854
21 m (27 to 101 m) or 13.0% ⫾ 4.4% (5.3% to 20.5%). This corresponded to lower mean values than the calculated ablation depth of 26 m. The mean epithelial thickness was 55.0 ⫾ 6.3 m (range 43.0 to 68.0 m; P ⫽ .14). The flap and residual stromal thickness decreased significantly compared with immediately postoperatively to mean values of 164 ⫾ 21 m (range 112 to 209 m) and 284 ⫾ 32 m (215 to 339 m), respectively (P⬍.001) (Table 3, Figure 3). At later examinations, the corneal, flap, and residual stromal thicknesses remained stable with no significant changes (Table 3, Figure 3). The epithelial thickness showed a slight but significant increase of 6 m (P⬍.001) after 5 months compared with the values on day 1 (Table 3). At 5 months, the mean residual stromal thickness was 282 ⫾ 36 m (212 to 350 m) corresponding to a relative residual stroma of 55.0% ⫾ 5.2% (range 43.0% to 64.0%). Although no patient had a residual stromal thickness less than 200 m during the follow-up, 7 eyes had a residual stromal thickness less than 250 m on corneal OCT measurement. Cumulative risk factors showed that eyes with a postoperative OCT corneal thickness less than 430 m (34 measurements, 36% of cases) were primarily those with a preoperative OCT corneal thickness below 500 m (82%) and had a 56% chance of a residual stromal thickness less than 250 m at a mean flap thickness of 161 m (range 112 to 195 m). Eyes with a residual stromal thickness less than 250 m in corneal OCT (21 measurements, 22% of cases) were primarily those with a preoperative corneal thickness below 500 m (86%) or a postoperative corneal thickness less than 430 m (91%) with a mean flap thickness of 173 m (range 154 to 194 m). Corrections of more than 8.0 D were made in only 29% of these eyes.
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Table 3. Central corneal OCT values before and after LASIK. Examination Time, Mean ⫾ SD (Range) Parameter
Preoperative
35 Min
1D
8D
35 D
160 D
516 ⫾ 26 (473 to 562)
555 ⫾ 47† (462 to 633)
448 ⫾ 39†‡ (392 to 509)
445 ⫾ 40 (383 to 513)
450 ⫾ 36 (391 to 513)
453 ⫾ 40 (389 to 511)
⌬ CCT* (m)
—
40 ⫾ 30 (–32 to 84)
–66 ⫾ 21 (–27 to –101)
–71 ⫾ 22 (–24 to –109)
–64 ⫾ 21 (–19 to –103)
–63 ⫾ 22 (–22 to –101)
⌬ CCT* (%)
—
7.6 ⫾ 5.7 (–6.4 to 17.4)
–13 ⫾ 4.4 (–5.3 to –20.5)
–14 ⫾ 4.6 (–4.4 to –21.8)
–13 ⫾ 4.4 (–3.6 to –20.8)
–12 ⫾ 4.5 (–4.3 to 20.1)
57 ⫾ 7.7 (48 to 78)
59 ⫾ 7.3 (49 to 76)
55 ⫾ 6.3 (43 to 68)
59 ⫾ 7.9 (48 to 78)
61 ⫾ 8.1 (43 to 78)
61 ⫾ 7.5‡ (46 to 79)
Flap (m)
—
211 ⫾ 28 (173 to 274)
164 ⫾ 21‡ (112 to 209)
168 ⫾ 18 (120 to 207)
169 ⫾ 15 (138 to 192)
171 ⫾ 21 (135 to 223)
Residual stroma (m)
—
344 ⫾ 48 (275 to 438)
284 ⫾ 32‡ (215 to 339)
276 ⫾ 38 (209 to 353)
281 ⫾ 39 (209 to 362)
282 ⫾ 36 (212 to 350)
Residual stroma (%)
—
67 ⫾ 6.9 (57 to 80)
55 ⫾ 4.4 (45 to 64)
53 ⫾ 5.7 (43 to 66)
55 ⫾ 5.4 (43 to 65)
55 ⫾ 5.2 (43 to 64)
CCT (m)
Epithelium (m)
Means ⫾ SDs CCT ⫽ central corneal thickness; LASIK ⫽ laser in situ keratomileusis; OCT ⫽ optical coherence tomography *Changes in the CCT compared to preoperatively † P⬍.005 compared with preoperative values (Wilcoxon signed rank test) ‡ P⬍.005 compared with 35 minutes or day 1 postoperative values (Wilcoxon signed rank test)
The mean reproducibility results of corneal OCT in LASIK are summarized in Table 4. Reproducibility was lowest for the determination of epithelial thickness. There was a transient slight decrease in reproducibility in all measurements of the corneal structures in the immediate postoperative period (Table 4).
Discussion Laser in situ keratomileusis involves the use of a microkeratome to create a thin lamellar corneal flap followed by excimer laser ablation of the corneal stroma and repositioning of the flap. Since refractive surgery candidates are healthy and have correctable vision, key criteria of LASIK are high standards of safety and stability and prevention of corneal complications by careful patient selection and therapeutic planning.1 Corneal imaging before and after LASIK is extremely important. Two-dimensional high-resolution imaging of the corneal structures after LASIK has been described with high-frequency US15 and confocal microscopy,16–19 but these are relatively invasive contact methods requiring a contact gel or an immersion bath with an uncertain effect due to epithelial compression or edema. The individual anatomical variability of corneal flap thickness and corneal stromal changes after LASIK has
also been reported with a retinal OCT at a wavelength of 840 nm, but this has certain limitations.20,21 In this prospective investigation, we evaluated the clinical application of slitlamp-adapted OCT for noncontact monitoring of the longitudinal changes in the corneal layers in LASIK. This OCT system had a wavelength of 1310 nm as the light source and was specifically designed for anterior segment applications.22–26 Slitlamp-adapted OCT allowed a 6.0 mm wide scan over the corneal cross-section compared with 1.0 to 3.8 mm scans in previous studies with retinal OCT,20,21 which also permitted peripheral measurements in selected cases. A wavelength longer than 840 nm improved resolution and definition of the corneal optical interfaces because of higher scattering in the tissues. In this clinical evaluation, slitlamp-adapted OCT confirmed reliable imaging of the cornea, epithelial layer, flap, and residual stroma in LASIK. Interface imaging was crucial in determining flap and residual stromal thickness with corneal OCT. Although the amount of light reflectivity was not quantified, the observed OCT imaging properties of the interface were distinguishable as early and late features. The early imaging properties were caused by slight surface irregularities from the movement of the oscillating blade, which
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Figure 2. (Wirbelauer)
Slitlamp-adapted corneal OCT (gray scale) of a patient before and after LASIK (myopic correction ⫺5.0 D [SE], ablation depth 78 m). a: Preoperative corneal OCT with a central thickness of 517 m. b: Corneal OCT 40 minutes after LASIK revealing surgically induced stromal edema. The central thickness values were 566 m for the cornea, 207 m for the flap, and 359 m for the residual stroma. c: On the first postoperative day, the values stabilized with a CCT of 457 m, a flap thickness of 160 m, and a residual stromal thickness of 294 m. Arrows demonstrate the optical interface.
caused ultrastructural changes and increased light scattering from irregular collagen fibrils and collagen fragments.28–31 A higher flap⫺interface reflectivity from microfolds in Bowman’s layer and an increase in scattering particles has also been confirmed by confocal microscopy, which was able to resolve the intrastromal changes at the cellular level.16–19 The late OCT imaging properties after LASIK were related to wound repair, which is a complex process exhibiting activated keratocytes at the wound margin and deposition of extracellular matrix material adjacent to the interface.16–19,29 However, after LASIK, the intrastromal interface is optically less well-defined than other 1856
corneal structures; there is minimal stromal disorganization and wound healing at the flap margins in animal and human studies.29,32–34 This might affect OCT imaging capabilities and discrimination of the microkeratome cut because of variable light reflectivities. With a retinal OCT, difficulties in interface determination after LASIK have been noted in cases with increased stromal tissue light scattering or after longer follow-up, with a decrease in discrimination of the intrastromal interface over time.20 Comparing the axial light reflectivity profile with the 2-dimensional corneal OCT image allowed us to correlate reflectivity changes with the interface bound-
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detection of this corneal substructure. The flap and residual stromal thickness reproducibility were ⬍5% with no deterioration after 5 months, which seems to be sufficient in the clinical setting. The microkeratome unit used in this study was automated, based on the oscillating blade principle designed to produce a surface-parallel keratotomy. The mean OCT flap thickness on day 1 was 164 ⫾ 21 m, which correlated well with the planned incision depth. However, the thickest flap was 223 m and the actual flap thickness has been shown to vary considerably depending on the microkeratome used.10–14 This illustrates that assumptions based on calculation of the flap thickness only can be misleading. Although intraoperative studies with US show a lower than predicted flap thickness,10–14 other studies with confocal microscopy report higher values for the same microkeratomes in the postoperative period.16,19 Thus, it seems there are marked differences between intraoperative and postoperative measurements10–14,37 and compression during suction and cutting may lead to lower flap thickness values intraoperatively. This was confirmed by a recent intraoperative study with online optical coherence pachymetry using the same microkeratome.27 In late postoperative measurements, the OCT flap thickness increased slightly by, on average, 7 m, but these changes were not significant. This contrasts with the partial regression and significant flap thickness increase noted with confocal microscopy,16 which was partly due to an increase in epithelial thickness. This is the only longitudinal study describing early postoperative changes immediately after LASIK. Noncontact OCT allowed us to study the immediate effects on the microstructure of the cornea without interfering with postoperative flap position and alignment. The OCT thickness values immediately after LASIK revealed
Figure 3. (Wirbelauer) The longitudinal OCT thickness changes of the cornea, epithelium, flap, and residual stroma in LASIK (mean ⫾ SD). Asterisks depict significant changes (P⬍.001) compared with preoperative (*) and immediately postoperative and day 1 (**) values.
aries and thus prevent higher variability in optical detection and a decrease in detection sensitivity. After LASIK, the interface was visible in all eyes for up to 15 months with good reproducibility; with retinal OCT, there was no visualization and an increase in failed measurements in 9.5% of eyes after 3 months.20 However, interface position variability and possible inclusion of the posterior border of the flap or the anterior border of the residual stroma in the thickness measurements must be considered. In our study, corneal reproducibility of slitlampadapted OCT at a wavelength of 1310 nm was similar to that with an OCT system at 830 nm.24 However, with OCT the CCT values were lower than those measured with US pachymetry, which is related to the differences between the refractive index and the speed of sound in corneal tissue.24 The epithelial reproducibility was better than at a wavelength of 830 nm,35,36 which indicates that a wavelength of 1310 nm improved the Table 4. Mean reproducibility of corneal OCT data in LASIK.
Examination Time Parameter
Preoperative
35 Min
1D
8D
35 D
160 D
Overall
CCT
4.90 (0.95)
5.09 (0.92)
3.76 (0.84)
4.19 (0.94)
5.04 (1.12)
4.02 (0.89)
4.50 (0.94)
Epithelium
3.24 (5.69)
7.54 (12.9)
5.92 (10.8)
4.8 (8.17)
4.03 (6.57)
4.44 (7.29)
4.99 (8.57)
Flap
7.34 (3.48)
6.82 (4.16)
5.63 (3.35)
4.97 (2.94)
6.50 (3.80)
6.25 (3.55)
Residual stroma
8.36 (2.43)
7.34 (2.59)
7.34 (2.66)
5.73 (2.04)
6.67 (2.37)
7.09 (2.42)
CCT ⫽ central corneal thickness; LASIK ⫽ laser in situ keratomileusis
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considerable corneal swelling from the microkeratome cut, surgical manipulations, and final irrigation procedures. The corneal hydration was linearly related to the corneal thickness, with a mean increase of 7.6% and a maximum swelling of 17.5%, but no significant changes in epithelial thickness. In some cases, the changes in stromal hydration interfered with the optical resolution of the corneal structures and interface visualization. However, rapid and complete recovery of the corneal values was noted on day 1. Contact-lens studies show that corneal deswelling measured with OCT occurs at a rate of approximately 5.6% per hour38 and deswelling from central corneal edema is 8.2% after 12 hours.39 Although changes in corneal hydration may affect the refractive index postoperatively40 and influence the measurements, the OCT values were relatively stable after day 1. This long-term stability of corneal OCT values after LASIK seems to allow a reliable assessment on day 1. Epithelial imaging with slitlamp-adapted OCT has been described.35,36 In our study, a small but significant increase in the anterior epithelial components was noted 5 months after LASIK compared with day 1, with no changes in the refractive results. After LASIK, a thickened epithelium was also found with confocal microscopy compared with normalized preoperative values19 found with a 50 MHz US pachymeter41 or other highresolution US techniques.15 Although post-LASIK epithelial thickening is lower than after surface ablation in PRK,42,43 corneal OCT could be important in studying epithelial and stromal factors involved in refractive regression after LASIK. Corneal OCT could also allow 2-dimensional visualization and quantification of intrastromal changes at the interface or interface complications such as diffuse lamellar keratitis, infection, epithelial ingrowth, and haze.36 Corneal OCT was also relevant in determining the amount of correction over the clinical course. On day 1, the measured ablation depth was significantly lower than the calculated depth by a mean of 26 m. Although the nominal ablation depth of the excimer laser can vary, these values are in contrast to intraoperative results27 and OCT values immediately after myopic PRK,26 in which the measured ablation depth is higher than the calculated ablation depth. The postoperative OCT results reveal that the presumed calculated ablation depth is probably lower, considering the postoperative corneal 1858
changes. This also confirms differences noted between the calculated magnitude of corneal surface change and the actual refraction change.40 The mean residual stromal thickness was 284 ⫾ 32 m on day 1, with no significant changes during the follow-up. An increase of 7.0 m in residual stromal thickness has been reported,20 but this increase could be related to a decrease in interface detection observed with retinal OCT. The lowest residual thickness in this study was 209 m; in 7 eyes, it was below 250 m with no clinical or topographic signs of corneal ectasia. Recent histological reports confirm that corneal ectasia, a major anatomical complication of LASIK, is caused by biomechanical corneal weakening after excessively deep central corneal ablation.5,7,34,44 Evaluation of the residual stromal thickness has been shown as crucial to prevent corneal ectasia, and safeguarding 250 m of stromal bed or 50% of the preoperative corneal thickness is the current standard of care to avoid this complication.2–4 Patients with lower residual stromal thickness measured intraoperatively by US pachymetry also had a higher posterior corneal elevation in LASIK enhancements.45 Ectasia has also occurred when more than 250 m of residual stroma remains,2,6 suggesting the phenomenon may be tissue dependent and involve metabolic processes.46 Of the reported cases of progressive corneal ectasia after LASIK, none had reliable measurements of residual bed thickness and multiple assumptions were required for estimating the values.2,3,5–7 Corneal OCT can supply the residual stromal thickness values to detect relevant biomechanical alterations and understand the corneal reactions after LASIK to prevent keratectasia. Major risk factors that could impair corneal stability are a cornea thinner than 500 m preoperatively, the flap thickness achieved by the microkeratome cut, a postoperative corneal thickness of less than 430 m, and refractive corrections greater than 8.0 D.2–9,37 In this study, the most common cumulative risk factors for a residual stromal thickness less than 250 m were a preoperative CCT less than 500 m or a postoperative corneal thickness less than 430 m. The flap thickness was not markedly increased in these eyes, and most had myopic corrections less than 8.0 D. Although studies with high-frequency US show that variability in the ability to predict residual stromal layer thickness postoperatively might be 30 m,47 our results indicate that
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in anatomically predisposed eyes, a residual stromal thickness of less than 250 m is probably more frequent than thought. This underscores the importance of a thorough preoperative evaluation and performing continuous intraoperative corneal thickness measurements during LASIK to avoid excessive thinning.27 In summary, slitlamp-adapted OCT allowed us to obtain preoperative and postoperative quantitative thicknesses of the cornea, epithelium, flap, and residual stroma in LASIK. Our study applied current knowledge about longitudinal changes in the corneal structures and helped in understanding the physiological effects and healing response of the cornea in LASIK. Comparing the optical thickness values of the corneal structures with the postoperative refraction may further improve surgeons’ LASIK nomograms, which seems particularly important in treating patients with thin corneas, performing LASIK enhancements, and planning high refractive corrections.
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